A morphological study of the glomerular lesions in chronic nephritis in the dog

Renal disease is of major importance in the dog, in terms of both morbidity and mortality. However, while the last two decades have seen great advances in the knowledge of Human and certain experimental animal nephropathies, very few in depth investigations of canine renal diseases have been published. In particular, despite the prominence of glomerular injury in many canine nephropathies, this process has largely been ignored. In Part 1 of this thesis, the literature on the most important canine nephropathies*viz; interstitial nephritis, glomerulonephritis, amyloidosis and suppurative nephropathies, was reviewed. An attempt was made to highlight the most important gaps in our knowledge with particular reference to pathogenesis of the lesions and morphological Changes in the glomeruli. The most common cause of renal failure in the dog is Chronic interstitial nephritis. In Part 2 of this thesis the first detailed combined light, electron and immunofluorescence microscopic study was carried out on this nephropathy as it is described in Britain. In addition, elution studies were performed to investigate further the immunopathology of the kidney. The diagnosis of chronic interstitial nephritis was found to cover a heterogeneous group of dogs. Of the 30 cases studied, 24 were probably the result of previous L. canicola infection. The remaining 6 cases appeared less likely to have resulted from L. canicola infection, but no positive evidence emerged to implicate another cause. However all 30 cases were alike in respect of immunopathology; neither autoantibodies nor immune complex deposition played a role in the severe renal scarring that characterized these cases. Recently a morphologically similar nephropathy, chronic glomerulonephritis, has been described in the dog. 10 cases were studied with the same techniques as listed above, and included in Part 2 of this thesis, for a comparative evaluation. In contrast to chronic interstitial nephritis, chronic glomerulonephritis is an immunologically mediated nephropathy. In all cases widespread deposits of immunoglobulin and bound complement were present in the glomeruli. In 9 cases granular deposits were found, a pattern highly suggestive of the involvement of immune complexes. In the remaining case linear deposits were present along the capillary walls a pattern suggestive of the presence of anti-glomerular basement membrane antibodies, but this was not confirmed by the elution studies. Despite this difference in aetiology, both nephropathies were Characterized by the Same progressive scarring and obliteration of the glomeruli. This process was described in detail in Part 2 of this thesis for the first time in the dog. The major components of this process were found to be a) thickening, wrinkling and duplication of both glomerular and capsular basement membranes, b) expansion of the mesangial cells and matrix, c) the deposition of fibrin obliterating capillaries and leading to the formation of capsular adhesions, d) the formation of collagen particularly in the urinary space. Fibrin deposition appeared to play a major role in the progression of glomerular scarring. This concept has been supported by studies on several experimental animal models, but none of this work had ever been carried out on the dog or the results applied to canine nephropathies. Therefore, Part 3 of this thesis was devoted to a combined light, electron and immunofluorescence microscopic study of two experimental canine nephropathies characterized by fibrin deposition in the glomeruli. In the first, a transient period of glomerular thrombosis, resulting from disseminated intravascular coagulation induced by Liquoid (sodium polyanetholsulphonate) injection, was followed by mild focal glomerular scarring. In the second, severe diffuse glomerular scarring followed a prolonged period of extensive fibrin deposition induced by nephrotoxic serum containing anti-glomerular basement membrane antibodies. Thus in both experimental immunological and non-immunological nephropathies glomerular scarring, similar to that encountered in both chronic interstitial nephritis and chronic glomerulonephritis, followed the deposition of fibrin in the glomeruli. This gave credibility to the view that fibrin deposition plays an important role in the progression of glomerular injury and obsolescence in chronic nephropathies of the dog